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- Title
Dermal Mast Cell Activation by Autoantibodies Against the High Affinity IgE Receptor in Chronic Urticaria.
- Authors
Niimi, Naomasa; Francis, David M.; Kermani, Faiz; O'Donnell, Brigid F.; Hide, Michihiro; Kobza-Black, Anne; Winkelmann, Richard K.; Greaves, Malcolm W.; Barr, Robert M.
- Abstract
Previous studies identified autoantibodies against the IgE high affinity receptor α-chain, FcεRIα, in sera of selected patients with severe chronic idiopathic urticaria. We have now determined the incidence of anti-FcεRIα autoantibodies in a group of 163 patients. Intradermal injection of autologous serum caused skin reactions indicative of mast cell degranulation in 98 (60%) patients. Based on histamine release from IgE-sensitized and nonsensitized basophil leukocytes of healthy donors, we detected anti- FcεRIα autoantibodies in sera from 38 (23%) urticaria patients and evidence for anti-IgE antibodies in a further nine patients. The sera that released histamine from basophils induced histamine release (4- 34%, n = 12) from mast cells in incubated skin slices. Protein-G affinity chromatography of sera demonstrated that mast cell histamine release was IgG- mediated. Preincubation of sera or the IgG fraction with a recombinant α-chain of FcεRIα inhibited histamine release from mast cells and basophils. Further studies with the mouse anti-human FcεRIα antibody 29C6 showed that mast cells and basophils were similarly sensitive to IgG-mediated direct cross-linking of FcεRIα, with 0.01-1.0 μ/ml 29C6 evoking histamine release in each case. These studies demonstrate that circulating levels of anti-FcεRIα autoantibodies mediate histamine release from skin mast cells <em>in vitro</em> and, taken together with <em>in vivo</em> evidence of mast cell degranulation following intradermal injection of autologous serum, support the concept that anti-FcεRIα autoantibodies are relevant to the pathogenesis of severe chronic urticaria in about 25% of patients.
- Subjects
URTICARIA; MAST cells; AUTOANTIBODIES; IMMUNOGLOBULIN E; CONNECTIVE tissue cells; IMMUNOGLOBULINS
- Publication
Journal of Investigative Dermatology, 1996, Vol 106, Issue 5, p1001
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1111/1523-1747.ep12338544